The present invention relates to dual chamber pacing systems, including rate responsive pacing systems, and more particularly to the employment of a time-dependent AV delay for pacing hearts in Congestive Heart Failure (CHF) with Dilated Cardiomyopathy (DCM).
Dual chamber pacing systems operating in the multi-programmable, DDD and DDDR pacing modes have been widely adopted in implantable dual chamber pacemakers and certain implantable cardioverter/defibrillators (ICDs) for providing atrial and ventricular (AV) synchronized pacing on demand. A DDD pacemaker implantable pulse generator (IPG) includes an atrial sense amplifier to detect atrial depolarizations or P-waves and generate an atrial sense event (A-EVENT) signal, a ventricular sense amplifier to detect ventricular depolarizations or R-waves and generate a ventricular sense event (V-EVENT) signal, atrial and ventricular pacing pulse generators providing atrial and ventricular pacing (A-PACE and V-PACE) pulses, respectively, and an operating system governing pacing and sensing functions. If the atria fail to spontaneously beat within a pre-defined time interval (atrial escape interval), the pacemaker supplies an A-PACE pulse to the atria through an appropriate lead system. The IPG supplies a V-PACE pulse to the ventricles through an appropriate lead system at the time-out of an AV delay timed from a preceding A-EVENT or generation of an A-PACE pulse unless a non-refractory V-EVENT is generated in response to an R-wave during the AV delay. Such AV synchronous pacemakers which perform this function have the capability of tracking the patient""s natural sinus rhythm and preserving the hemodynamic contribution of the atrial contraction over a wide range of heart rates.
The rate-adaptive DDDR pacing mode functions in the above-described manner but additionally provides rate modulation of a pacing escape interval between a programmable lower rate and an upper rate limit (URL) as a function of a physiologic signal or rate control parameter (RCP) developed by one or more physiologic sensors and related to the need for cardiac output. In the DDDR pacing mode, reliance on the intrinsic atrial heart rate is preferred if it is appropriately between the URL and the programmed lower rate. At times when the intrinsic atrial rate is inappropriately high, a variety of xe2x80x9cmode switchingxe2x80x9d schemes for effecting switching between tracking modes and non-tracking modes (and a variety of transitional modes) based on the relationship between the atrial rate and the sensor derived pacing rate have been proposed as exemplified by commonly assigned U.S. Pat. No. 5,144,949, incorporated herein by reference in its entirety.
The DDD and DDDR pacing modes were initially perceived to be of greatest benefit to cardiac patients whose hearts have an intact sinoatrial (SA) node that generates the atrial depolarizations detectable as P-waves, but also suffer defective A-V conduction, or AV block, wherein the ventricles fail to depolarize in synchrony with the atria. The DDD pacing mode paces the ventricles in synchrony with the atria after a timed out AV delay and is generally adequate to restore cardiac output for sedentary patients. Active patients with Sick Sinus Syndrome (SSS) have an atrial rate which can be sometimes appropriate, sometimes too fast, and sometimes too slow. For SSS patients, the DDDR pacing mode provides some relief by pacing the atria and ventricles at a physiologic rate determined by an algorithm responsive to the RCP indicative of the patient""s metabolic needs.
A loss of A-V electrical and mechanical synchrony can result in series of asynchronous atrial and ventricular depolarizations at independent rates that periodically result in an atrial depolarization that closely follows a ventricular depolarization. When this occurs, the left atrium contracts against a closed mitral valve, resulting in impeded venous return from the pulmonary vasculature due to increased atrial pressure and possibly even retrograde blood flow into the pulmonary venous circulation. As a result, the volume and pressure in the pulmonary venous circulation rise. Increased pulmonary pressures may lead to pulmonary congestion and dyspnea. Distention of the pulmonary vasculature may be associated with peripheral vasodilation and hypotension. In addition, the concomitant atrial distention is associated with increased production of atrial natriuretic factor and increases the susceptibility to atrial arrhythmias and possibly rupture of the atrial wall. Finally, turbulence and stagnation of blood within the atrium increase the risk of thrombus formation and subsequent arterial embolization. Maintenance of AV mechanical synchrony is therefore of great importance as set forth in greater detail in commonly assigned U. S. Pat. No. 5,626,623, incorporated herein by reference in its entirety.
Theoretically, AV synchrony is best maintained during dual chamber cardiac pacing by setting the AV delay interval in a physiological range related to the spontaneous atrial rate or the sensor derived rate, depending on which is the controlling pacing mode. However, while xe2x80x9cphysiologicalxe2x80x9d AV delays may ensure right heart AV electrical synchrony, in patients with significant interatrial and/or interventricular conduction delays, left heart electrical and mechanical synchrony, and thus hemodynamic performance, may be significantly compromised.
The maintenance of AV mechanical synchrony is of vital importance in patients with compromised cardiac function, including CHF, DCM, hypertrophic cardiomyopathy, hypertensive heart disease, restrictive cardiomyopathy, and other disorders that are characterized by significant diastolic dysfunction. In such patients, passive ventricular filling is reduced due to poor ventricular compliance and incomplete or delayed relaxation. Consequently, there is increased reliance on atrial contraction for ventricular filling sufficient to achieve adequate stroke volume and maintain low atrial and pulmonary pressure.
Carefully controlled AV delays have been found to be beneficial to increase cardiac output of hearts of certain patients that exhibit cardiomyopathy and forms of CHF, and in particular Hypertrophic Obstructive Cardiomyopathy (HOCM). HOCM is characterized by a narrowed left ventricular outflow tract (LVOT), which causes a significant increase in the left ventricular end systolic pressure. The narrowed LVOT is caused by an increased thickness of the interventricular septum which obstructs blood flow during systole, the time of cardiac ejection.
Symptomatic improvement of patients with HOCM can be obtained in some cases with the use of standard pharmacotherapy. However, drugs in use for this therapy have disadvantages which have been cited in the literature. Likewise, surgical intervention, e.g., septal myectomy or mitral valve replacement, is another optional treatment. However, such surgical treatments carry a significant operative mortality and have not been shown to alter the natural history of the disease. See, for example, xe2x80x9cPermanent Pacing As Treatment For Hypertrophic Cardiomyopathy,xe2x80x9d by Kenneth M. McDonald et al., American Journal of Cardiology, Vol. 68, pp. 108-110, July 1991.
The value of dual chamber cardiac pacing and treatment of patients suffering from HOCM has been recognized in the literature. Studies have indicated that patients suffering from HOCM may benefit from a specific mode of dual chamber pacing, wherein a ventricular pacing pulse is delivered in timed synchrony with the sensed or paced atrial depolarization. Pacing the right ventricular apex before spontaneous atrio-ventricular conduction activates the ventricles is understood to alter the ventricular septal activation pattern. Since the right ventricle is caused to contract first, it pulls the septum toward the right ventricle thereby reducing the LVOT obstruction. The literature uniformly acknowledges the potential advantages of synchronized AV pacing for HOCM patients, stressing the importance of achieving ventricular capture. Causing xe2x80x9ccomplete ventricular capturexe2x80x9d is important to obtain the above-described septal movement, while selecting the longest AV delay that results in complete ventricular capture is important in order to maximize the atrial contribution to ventricular filling. See, for example, commonly assigned U.S. Pat. No. 5,507,782, and the literature articles referenced therein. The delivered pacing pulse should provide xe2x80x9cpre-excitation,xe2x80x9d i.e., depolarization of the ventricular apex before the septum. This altered pattern of septal contraction, as well as optimal left ventricular filling, is generally recognized as being important to this mode of pacemaker treatment.
The literature suggests that the AV delay should be set at the longest duration that maintains ventricular capture at different exercise levels. See the above-cited McDonald article. It has been suggested that the AV delay that allows for maximal pre-excitation of the ventricle by the pacing pulse can be selected by determining the AV delay that produces the widest paced QRS complex duration, as seen on a surface electrocardiogram. See, for example, xe2x80x9cImpact of Dual Chamber Permanent Pacing in Patients With Obstructive Hypertrophic Cardiomyopathy With Symptoms Refractory to Verapamil and beta.-Adrenergic Blocker Therapy,xe2x80x9d by Fananapazir et al., Circulation, Vol. 8, No. 6, June 1992, pp. 2149-2161.
The prior art techniques for AV synchronous pacing of HOCM patients recognize the necessity to periodically evaluate the pacing AV delay. The patient""s spontaneous atrio-ventricular conduction time generally will change with heart rate, i.e., from rest to exercise. Moreover, simultaneous drug treatment such as beta blockers may also modify A-V conduction time and require renewed evaluation of the AV delay. The importance of periodically making an accurate determination of the optimized pacing AV delay thus takes on significance. If the AV delay is adjusted to a value which is too short, in order to ensure complete ventricular capture, the atrial contribution to ventricular filling may be compromised. However, if the AV delay is adjusted to too great a value, ventricular capture is compromised, and there may be episodes of no ventricular pacing or the ventricular pace may not contribute the best possible reduction of the LVOT obstruction. Accordingly, it is important in this therapy to be able to continuously or periodically adjust the AV delay to optimize it for HOCM therapy. Commonly assigned U.S. Pat. Nos. 5,534,506, 5,626,620, 5,626,623, 5,716,383, and 5,749,906 disclose ways of optimizing the pacing AV delay.
However, AV synchronized pacing of CHF hearts exhibiting DCM (a CHF/DCM heart) do not necessarily benefit from the variable, and typically long AV delay that is determined to be optimal for HOCM patients. Frequently, CHF/DCM hearts exhibit intrinsic A-V (alternatively referred to as P-Q) conduction intervals between 180 ms-260 ms with LBBB patterns or Inter-Ventricular Conduction Delay (IVCD), and widened QRS complexes  greater than 120 ms, and also exhibit A-V conduction defects, including 1xc2x0 AV Block (AVB). In time the 1xc2x0 AV Block can degenerate to 2xc2x0 AV Block or 3xc2x0 AV Block. Widened QRS Complexes ( greater than 120 ms), caused either by LBBB, IVCD, or RV paced evoked response, represent a significant delay in LV electrical activation and thus a significant delay in LV mechanical activation. FIG. 7. illustrates the intrinsic cardiac sinus rhythm of a patient""s heart (at a 65 bpm heart rate, for example) with intrinsic LBBB, 1xc2x0 AV block, LA to LV asynchrony, and reduced LV filling time with subsequent fusion of transmitral inflow rapid filling phase (E wave) and active filling phase (A wave).
Optimal AV delay timing is obtained when the onset of LV contraction occurs immediately upon completion of the LA contribution (Left Atrial Kick) in late diastole. At this moment, the LV filling (preload) is maximum, and the Frank Starling Relationship between LV stretch and LV contraction is the greatest. This will result in maximum LV stroke volume ejection, and thus maximum Cardiac Index/Cardiac Output to be realized. To realize this exact Atrial-Ventricular Sequential timing, the AV delay must be fully optimized. FIG. 8. illustrates the cardiac rhythm of a heart having a minor LA to LV asynchrony and sub-optimal, too long, AV delay timing, partial fusion of E and A waves, and increased LV Filling (LVFT). Any delay between the completion of atrial contribution and the start of LV contraction (indicated as xcex4 in FIG. 8), can lead to xe2x80x9cPre-Systolicxe2x80x9d mitral regurgitation, resulting in loss of effective LV filling and thus loss of LV stroke volume and reduced cardiac output. In addition, a too long AV delay reduces the diastolic time available for proper LVFT) as observed on the diastolic Transmitral Inflow Pattern, resulting in a fusion (competitive action) of the E wave vs. the A wave of the Mitral Flow Relationship (also shown in FIG. 8.).
FIG. 9. illustrates a desirable exact LA to LV synchrony restored in a cardiac rhythm due to a short, optimized AV delay, LV contraction occurring upon completion of A wave, and maximum diastolic LVFT. A short, optimized AV delay, however, will allow maximum defusion of E and A waves, and a maximum LVFT to be realized at any given heart rate, contributing to increased cardiac output (see FIG. 9). Recent findings of studies of such hearts has determined that each CHF/DCM heart has an optimal short AV delay that generates the highest cardiac output and provides the most physiologic hemodynamics as measured using echocardiography. See, xe2x80x9cEffect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failurexe2x80x9d by Auricchio A, Stellbrink C, et al., Circulation 1999, June 15;99(23):2993-3001.
Short AV delays in the range of 60 ms-140 ms appear to be superior to the 180 ms-240 ms AV delays that have been typically either preset or calculated using the algorithms described above for determining the AV delay for HOCM hearts. Consequently, it is recommended that the AV delays of the implanted DDD and DDDR pacemakers be set to the relatively short AV delays determined in testing the cardiac output at differing AV delays.
But, abruptly commencing AV pacing with such a short AV delay represents a significant change in the function of and load on the CHF/DCM heart wherein, prior to pacing, the ventricles depolarized after a longer intrinsic AV delay. FIG. 1 illustrates the abrupt change from a chronic, prolonged, intrinsic AV delay of 225 ms, for example, exhibited in a CHF/DCM heart that is well above the normal, healthy heart, intrinsic AV delay of 125 ms. After years of gradually increasing intrinsic AV delay, the patient""s heart is subjected to a programmed chronic AV delay of 100 ms, for example, for a sense AV delay (SAV delay) or a pace AV delay (PAV delay) or both.
This means that the heart is suddenly forced to change from a situation with long AV to short AV delay. In the long AV delay situation, the filled left ventricle has more time to let blood flow back into the left atrium before contraction starts (mitral regurgitation), which on the one hand reduces the cardiac output but on the other hand may serve as a kind of xe2x80x98pressure relief valvexe2x80x99 to limit the LV end diastolic pressure, which is extremely elevated in these patients. In the short AV delay situation, the maximum cardiac output requirements (exact synchronized filling of LV, optimal LV filling period, and optimal preloading of LV) are met, but the pressure may become high in the LV that is not xe2x80x98usedxe2x80x99 to that.
The present invention is therefore particularly directed to a method and apparatus for avoiding or alleviating stress of a patient""s heart induced by programming a relatively short AV delay in comparison to an intrinsic, prolonged AV delay. In accordance with the present invention, a Time-Adaptive AV delay (TA-AV delay) determining algorithm is started upon implantation of a DDD or DDDR pacing system in a patient having a CHF/DCM heart. At or about the time of implantation, the AV delay is initially set at a relatively long starting or initial AV delay that may be correlated with any intrinsic AV delay that the patient""s heart exhibits. Thereafter, the TA-AV delay is incrementally decreased or decrement over a post-implant Time-Adaptive (TA) period of time of hours, days or weeks until a programmed, relatively shorter, AV delay is reached. Then, the programmed, chronic, AV delay is maintained.
The TA-AV delay is either linearly or non-linearly decremented in time interval from the initial AV delay to the chronic AV delay in decrement steps over the post-implant TA period. Preferably, a separate SAV delay is commenced by the A-EVENT signal and a PAV delay is commenced at time-out of an atrial pace escape interval and delivery of the A-PACE pulse. The present invention may be implemented in such a way that the Time-Adaptive feature is programmed on to operate for establishing a TA-SAV delay or a TA-PAV delay or both during the post-implant period.
In this way, the heart gradually adapts to the optimal chronic AV delay and stress is reduced. This gradual process may aid in the remodeling process of the CHF/DCM heart. The process of remodeling is a gradual adaptation of the muscle cells of the heart to a new situation of different wall stresses, volume loading, and/or contraction patterns. Some relevant references include the following: xe2x80x9cAsynchronous Electrical Activation Induces Asymmetrical Hypertrophy of the Left Ventricular Wallxe2x80x9d, by Oosterhout, Prinzen, et al., Circulation, 1998;98:588-595; and xe2x80x9cRedistribution of myocardial fiber strain and blood flow by asynchronous activationxe2x80x9d by Prinzen et al., American Journal of Physiology, 1990;259:H300-H308.
Preferably, the TA-AV delay is further modified or altered during the TA period to provide a more physiologic AV delay under certain conditions where a need for increased cardiac output causes the pacing system to increase its pacing rate. In this case, the TA-AV delay is calculated but can be temporarily altered by a rate response pacing algorithm.